Hybrid Imaging Agents for Pretargeting Applications Based on Fusarinine C-Proof of Concept.

Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a -cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo.

Pretargeted Imaging with Gallium-68-Improving the Binding Capability by Increasing the Number of Tetrazine Motifs.

The inverse electron-demand Diels-Alder reaction between 1,2,4,5-tetrazine (Tz) and -cyclooct-2-ene (TCO) has gained increasing attraction among extensive studies on click chemistry due to its exceptionally fast reaction kinetics and high selectivity for in vivo pretargeting applications including PET imaging. The facile two-step approach utilizing TCO-modified antibodies as targeting structures has not made it into clinics yet. An increase in the blood volume of humans in comparison to mice seems to be the major limitation.